St. Ambrose was born in Trier, Germany, in AD 339, and he was the youngest of three children. After his father died, his mother and older sister reared Ambrose in a palace in Rome. Ambrose grew in secular knowledge, as well as in piety through his mastery of Greek and literature. Later, he devoted his interest to the study and practice of law. He soon distinguished himself by his skill and persuasiveness in court. Anicius Probus brought him into the Prefect's council and later helped him become appointed to Consularis AEmiliae in Circa AD 370, in Milan. Ambrose's honest and gentle administration earned him widespread high esteem.

There had been religious chaos in Milan between the orthodox Christians and the Arian Fraction. Milan had no official bishop during this time when St. Ambrose stepped up to help keep order in the city. He kept the peace by delivering a speech about peace and moderation. While doing so, a young child's voice cried out, "Ambrose for bishop!" The entire assembly instantly repeated the cry, and Ambrose was unanimously acclaimed to the office of Bishop of Milan by both the clergy and the people. Ambrose accepted the position only after Emperor Valentinian endorsed the election. On December 7, AD 374 (the day on which the East and West annually honor his memory), St. Ambrose was consecrated as Bishop of Milan. He was thirty-five years old and served the Church for twenty-three active years, proving to be a Christian bishop's ideal model.

Ambrose practiced a very pious and modest lifestyle. He ate sparingly and spent long nocturnal vigils in prayer. Every day he offered Mass for his people. His tireless dedication and meticulous habits helped him respond to his correspondents personally and write his daily thoughts, many of which resulted in the invaluable books and hymns he composed. His eloquent Sunday discourses drew immense crowds to the Basilica as he spoke from the heart rather than written sermons. He spoke about concise rules of conduct and interpretation of the Scriptures as applied to the current generation during his sermons. Those sermons gained him the most notable convert, Aurelius Augustinus (later known as St. Augustine, who became the Bishop of Hippo Regius in North Africa). Ambrose's intervention helped Christianity prevail in the conflict between Eastern and Western Roman Empires concerning the reinstatement of paganism over Christianity.

As a way to emphasize his extraordinary capacity to do work, Ambrose's secretary once stated, "No human frame could long endure the incessant activity of an Ambrose." When Ambrose the Bishop of Milan was seriously ill, he lay with extended arms in imitation Jesus, his expiring Master, who also appeared to him in person. On Good Friday, April 5, AD 397, right after receiving the Body of Christ, he peacefully breathed his last. As he desired, Ambrose was laid to rest in his beloved Basilica by the side of the holy martyrs, Gervasius and Protasius. In the year AD 835 one of his successors, Angilbert II, placed the relics of the three saints in a porphyry sarcophagus under the altar, where they were later rediscovered in AD 1864.